The primary objective is to determine if the administration of a single dose of oral ondansetron (an anti-vomiting medication), compared to placebo, results in a reduction in intravenous (IV) rehydration therapy in children presenting for emergency department care with vomiting and diarrhea in Pakistan.

IV rehydration is defined as the IV administration of ≥20 ml/kg over 4 hours an isotonic fluid for the purpose of rehydration within 72 hours of randomization. This definition allows for the occurrence of the primary outcome in children who receive maintenance plus replacement of losses and not simply those who receive a fluid bolus. This will not include those who simply receive maintenance fluids (e.g. 4 ml/kg/hr for those weighing < 10 kg). This will also enable us to exclude children who undergo IV insertion for the purpose of medication administration. IV rehydration is a powerful marker of treatment failure, a decrease in which is likely to impact practice and influence decision makers since it is drastically more expensive that ORT, it is painful and is associated with a greater risk of adverse events.

Secondary Outcome Measures:

The proportion of children who vomit during the 4 hour observation period [ Time Frame: within 4 hour observation period after randomization ] [ Designated as safety issue: No ]

The frequency of vomiting during the 4 hour observation period [ Time Frame: within 4 hour observation period after randomization ] [ Designated as safety issue: No ]

Eligible children will receive one weight based (0.13 - 0.26 mg/kg) dose of an oral ondansetron disintegrating tablet. Subsequent therapy will be in accordance with World Health Organization guidelines as dictated by the child's hydration status.

Other Name: Zofran

Placebo Comparator: Placebo (sugar pill)

Drug: Placebo

Eligible children will receive one dose of an oral disintegrating Placebo (sugar pill) tablet. Subsequent therapy will be in accordance with World Health Organization guidelines as dictated by the child's hydration status.

Other Name: Sugar Pill

Detailed Description:

Gastroenteritis remains one of the most common causes of morbidity and mortality in children <5 years of age worldwide. A critical factor in the reduction in mortality over the past 30 years has been the introduction of oral rehydration therapy (ORT) for the treatment of dehydration.

However, its use has stagnated in many low- and middle-income countries (LMIC) where many children lack access to alternatives such as intravenous (IV) rehydration. When such children have fluid losses that cannot be replaced orally due to intractable vomiting, death is common. Finding a safe, non-invasive, and effective strategy to reduce vomiting in children would substantially decrease the need for IV rehydration and hence morbidity and mortality in LMICs. Although antiemetic agents are included in the WHO list of Essential Medicines, their use in children with gastroenteritis is not endorsed by the World Health Organization (WHO). Concerns include a lack of evidence that antiemetic agents can improve outcomes and that they are associated with dangerous side effects. However, in high-income settings, studies on ondansetron, an antiemetic agent, have demonstrated that it can reduce vomiting, IV rehydration, and hospitalization. Recent reviews by prominent organizations (e.g. International child Health Review Collaboration; the Committee on the Selection and Use of Essential Medicines) have indicated an interest in ondansetron use in children with gastroenteritis, and they have concluded that further evidence is required. This trial aims to determine if the administration of a single dose of oral ondansetron results in improved outcomes in children brought for emergency department care with vomiting and diarrhea in Pakistan.

Two trials will be conducted under the umbrella of one study. The proposed trials will be identical with the exception of the severity of dehydration at enrollment (either "some" or none "well").

This study will have immediate impact on patient management. Based on the results, it will be discovered if oral ondansetron plays a role in reducing the need for intravenous rehydration in children with gastroenteritis in Pakistan. As ondansetron is now available in generic formulations, and is relatively inexpensive, it is anticipated that if this study is positive, ondansetron will be considered for inclusion in the WHO - gastroenteritis care package. This could ultimately lead to a decrease in the need for intravenous rehydration in children in countries such as Pakistan. Moreover, these findings will lead to a subsequent study evaluating its potential benefit in outreach communities where treatments such as intravenous rehydration are unavailable.

Eligibility

Ages Eligible for Study:

6 Months to 59 Months

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Age 6 - 59 months (0.5 - 5 years)

Symptoms consistent with gastroenteritis (must have a & b)

a. 1 episode of nonbilious, nonbloody vomiting within the 4 hours preceding triage i. The requirement for only 1 vomiting episode is based on prior work which similarly required 1 vomiting episode within 4 hours of triage. The later study reported a 17% absolute reduction in the use of IV rehydration. The vast majority of children seeking care and enrolled in the aforementioned study had a significantly greater number of vomiting episodes in the preceding 24 hour (mean >9 episodes).

b. Presence of ≥ 1 episode of diarrhea during the illness i. We require the presence of only 1 diarrheal stool to enhance our probability of enrolling children with enteritis (as opposed to other diagnoses). In fact, of the 8 RCTs performed using antiemetics in children with gastroenteritis in developed countries, only 1 even required the presence of any diarrhea as part of the eligibility criteria (and that study required a single diarrheal stool).

Presence of NO dehydration (NO=not enough signs to classify as some or severe dehydration)

Exclusion Criteria:

Weight <8 kg

Vomiting or diarrhea for > 7 days

Malnutrition: The World Health Organization (WHO) definition will be employed - weight for height below -3z scores of the median WHO growth standards

Known hypersensitivity to ondansetron or any serotonin receptor antagonist

History or family history of prolonged QT syndrome

Taking apomorphine or any medication that is generally accepted as having a risk of causing torsades de pointes

Patients previously enrolled in the study

Follow-up will not be possible

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01870635